Biomedical subjects

Zheng Yuan

Publications and source records attributed to Zheng Yuan.

At least 19 recordsLinked to original sources

PubMed2007

Comparing the small sample performance of several variance estimators under competing risks.

We examine several variance estimators for cumulative incidence estimators that have been proposed over time, some of which are derived from asymptotic martingale or counting process theory, and some of which are developed from the moments of the multinomial distribution. There is little published work comparing these variance estimators, largely because the variance estimators are algebraically complex and difficult to interpret and all but one have yet to be programmed for a standard statistical package. Through simulation and application to real data, we compare the performance of six variance estimators in relation to each other and the bootstrap in order to confirm earlier reports of their performance and to provide future direction toward their application. We find that the multinomial-moment-based estimators have performance close to that of the bootstrap, and are quite accurate for estimating the variance, even in samples of 20 subjects. All but one of the martingale theory-based estimators tend to perform poorly in small samples, tending to either overestimate or underestimate the empirical variance in samples of fewer than 100 subjects.

Analysis of Variance↗

PubMed2006

The rice tapetum degeneration retardation gene is required for tapetum degradation and anther development.

In flowering plants, tapetum degeneration is proposed to be triggered by a programmed cell death (PCD) process during late stages of pollen development; the PCD is thought to provide cellular contents supporting pollen wall formation and to allow the subsequent pollen release. However, the molecular basis regulating tapetum PCD in plants remains poorly understood. We report the isolation and characterization of a rice (Oryza sativa) male sterile mutant tapetum degeneration retardation (tdr), which exhibits degeneration retardation of the tapetum and middle layer as well as collapse of microspores. The TDR gene is preferentially expressed in the tapetum and encodes a putative basic helix-loop-helix protein, which is likely localized to the nucleus. More importantly, two genes, Os CP1 and Os c6, encoding a Cys protease and a protease inhibitor, respectively, were shown to be the likely direct targets of TDR through chromatin immunoprecipitation analyses and the electrophoretic mobility shift assay. These results indicate that TDR is a key component of the molecular network regulating rice tapetum development and degeneration.

Amino Acid Sequence↗

PubMed2006

The floral organ number4 gene encoding a putative ortholog of Arabidopsis CLAVATA3 regulates apical meristem size in rice.

To understand the molecular mechanism regulating meristem development in the monocot rice (Oryza sativa), we describe here the isolation and characterization of three floral organ number4 (fon4) alleles and the cloning of the FON4 gene. The fon4 mutants showed abnormal enlargement of the embryonic and vegetative shoot apical meristems (SAMs) and the inflorescence and floral meristems. Likely due to enlarged SAMs, fon4 mutants produced thick culms (stems) and increased numbers of both primary rachis branches and floral organs. We identified FON4 using a map-based cloning approach and found it encodes a small putatively secreted protein, which is the putative ortholog of the Arabidopsis (Arabidopsis thaliana) CLAVATA3 (CLV3) gene. FON4 transcripts mainly accumulated in the small group of cells at the apex of the SAMs, whereas the rice ortholog of CLV1 (FON1) is expressed throughout the SAMs, suggesting that the putative FON4 ligand might be sequestered as a possible mechanism for rice meristem regulation. Exogenous application of the peptides FON4p and CLV3p corresponding to the CLV3/ESR-related (CLE) motifs of FON4 and CLV3, respectively, resulted in termination of SAMs in rice, and treatment with CLV3p caused consumption of both rice and Arabidopsis root meristems, suggesting that the CLV pathway in limiting meristem size is conserved in both rice and Arabidopsis. However, exogenous FON4p did not have an obvious effect on limiting both rice and Arabidopsis root meristems, suggesting that the CLE motifs of Arabidopsis CLV3 and FON4 are potentially functionally divergent.

Amino Acid Sequence↗

PubMed2006

Synthesis, crystal structures, linear and nonlinear optical properties, and theoretical studies of (p-R-phenyl)-, (p-R-phenylethynyl)-, and (E)-[2-(p-R-phenyl)ethenyl]dimesitylboranes and related compounds.

The (p-R-phenyl)dimesitylboranes (R=Me(2)N, MeO, MeS, Br, I), (p-R-phenylethynyl)dimesitylboranes (R=Me(2)N, MeO, MeS, H), (E)-[2-(p-R-phenyl)ethenyl]dimesitylboranes (R=Me(2)N, H(2)N, MeO, MeS, H, CN, NO(2)), (E)-[2-(2-thienyl)ethenyl]dimesitylborane, and (E)-[2-(o-carboranyl)ethenyl]dimesitylborane have been prepared through the reaction of the appropriate p-R-phenyl- and p-R-phenylethynyllithium reagents with dimesitylboron fluoride and by hydroboration of the appropriate p-R-phenylacetylene, 2-ethynylthiophene, and o-ethynylcarborane with dimesitylborane. Their UV/Vis absorption and emission spectra have been recorded in a range of solvents with the fluorescence maxima of the donor-substituted compounds in particular exhibiting large bathochromic shifts in highly polar solvents, indicative of charge transfer leading to large dipole moments in the excited state. The molecular structures of the (p-R-phenyl)dimesitylboranes (R=Me(2)N, MeO, MeS, Br, I), the (E)-[2-(p-R-phenyl)ethenyl]dimesitylboranes (R=Me(2)N, H(2)N MeO, MeS, H), (p-R-phenylethynyl)dimesitylborane (R=Me(2)N), and (E)-[2-(2-thienyl)ethenyl]dimesitylborane, which have been determined from single-crystal X-ray diffraction measurements, offer evidence of increased conjugation in the ground state with increased donor strength of the R substituent. Their first- and second-order molecular hyperpolarizabilities have been obtained from EFISH and THG measurements, the first-order hyperpolarizabilities being largest for the strongest R-substituent donors. AM1 calculations have been performed on these compounds, showing reasonable agreement with the experimentally obtained bond lengths and hyperpolarizabilities, as well as on several related hypothetical compounds containing multiple C==C bonds, most of which are proposed to have even larger hyperpolarizabilities.

Journal Article↗

PubMed2006

Prediction of cis/trans isomerization in proteins using PSI-BLAST profiles and secondary structure information.

BACKGROUND: The majority of peptide bonds in proteins are found to occur in the trans conformation. However, for proline residues, a considerable fraction of Prolyl peptide bonds adopt the cis form. Proline cis/trans isomerization is known to play a critical role in protein folding, splicing, cell signaling and transmembrane active transport. Accurate prediction of proline cis/trans isomerization in proteins would have many important applications towards the understanding of protein structure and function. RESULTS: In this paper, we propose a new approach to predict the proline cis/trans isomerization in proteins using support vector machine (SVM). The preliminary results indicated that using Radial Basis Function (RBF) kernels could lead to better prediction performance than that of polynomial and linear kernel functions. We used single sequence information of different local window sizes, amino acid compositions of different local sequences, multiple sequence alignment obtained from PSI-BLAST and the secondary structure information predicted by PSIPRED. We explored these different sequence encoding schemes in order to investigate their effects on the prediction performance. The training and testing of this approach was performed on a newly enlarged dataset of 2424 non-homologous proteins determined by X-Ray diffraction method using 5-fold cross-validation. Selecting the window size 11 provided the best performance for determining the proline cis/trans isomerization based on the single amino acid sequence. It was found that using multiple sequence alignments in the form of PSI-BLAST profiles could significantly improve the prediction performance, the prediction accuracy increased from 62.8% with single sequence to 69.8% and Matthews Correlation Coefficient (MCC) improved from 0.26 with single local sequence to 0.40. Furthermore, if coupled with the predicted secondary structure information by PSIPRED, our method yielded a prediction accuracy of 71.5% and MCC of 0.43, 9% and 0.17 higher than the accuracy achieved based on the singe sequence information, respectively. CONCLUSION: A new method has been developed to predict the proline cis/trans isomerization in proteins based on support vector machine, which used the single amino acid sequence with different local window sizes, the amino acid compositions of local sequence flanking centered proline residues, the position-specific scoring matrices (PSSMs) extracted by PSI-BLAST and the predicted secondary structures generated by PSIPRED. The successful application of SVM approach in this study reinforced that SVM is a powerful tool in predicting proline cis/trans isomerization in proteins and biological sequence analysis.

Databases, Protein↗

PubMed2006

Prediction of protein continuum secondary structure with probabilistic models based on NMR solved structures.

BACKGROUND: The structure of proteins may change as a result of the inherent flexibility of some protein regions. We develop and explore probabilistic machine learning methods for predicting a continuum secondary structure, i.e. assigning probabilities to the conformational states of a residue. We train our methods using data derived from high-quality NMR models. RESULTS: Several probabilistic models not only successfully estimate the continuum secondary structure, but also provide a categorical output on par with models directly trained on categorical data. Importantly, models trained on the continuum secondary structure are also better than their categorical counterparts at identifying the conformational state for structurally ambivalent residues. CONCLUSION: Cascaded probabilistic neural networks trained on the continuum secondary structure exhibit better accuracy in structurally ambivalent regions of proteins, while sustaining an overall classification accuracy on par with standard, categorical prediction methods.

Algorithms↗

PubMed2006

Embryogenesis and seed development in Sinomanglietia glauca (Magnoliaceae).

The development of the floral bud, especially the ovule and seed coat, of Sinomanglietia glauca was observed. Floral buds were covered by eight to nine hypsophyll pieces. The hypsophyll nearest the tepal was closed completely and characterized by two arrays of densely stained cells with dense cytoplasm, which split longitudinally at flowering. The perianth consisted of 16 tepals arranged in three whorls. The gynoecium was composed of numerous apocarpous carpels; the ovule was anatropous with two integuments. Embryogenesis was of the Polygonum type, and the endosperm was nuclear. The inner integument degenerated during seed development. The seed of S. glauca had an endotestal seed coat comprised of a sclerotic layer derived from the inner adaxial epidermis of the outer integument and a sarcotesta derived mainly from the middle cells between the inner and outer epidermis of the outer integument. The embryo developed normally, so embryogenesis is not the cause of difficult regeneration.

Flowers↗

PubMed2006

Predicting the solvent accessibility of transmembrane residues from protein sequence.

In this study, we propose a novel method to predict the solvent accessible surface areas of transmembrane residues. For both transmembrane alpha-helix and beta-barrel residues, the correlation coefficients between the predicted and observed accessible surface areas are around 0.65. On the basis of predicted accessible surface areas, residues exposed to the lipid environment or buried inside a protein can be identified by using certain cutoff thresholds. We have extensively examined our approach based on different definitions of accessible surface areas and a variety of sets of control parameters. Given that experimentally determining the structures of membrane proteins is very difficult and membrane proteins are actually abundant in nature, our approach is useful for theoretically modeling membrane protein tertiary structures, particularly for modeling the assembly of transmembrane domains. This approach can be used to annotate the membrane proteins in proteomes to provide extra structural and functional information.

Cell Membrane↗

PubMed2006

Duplication and expression analysis of multicopy miRNA gene family members in Arabidopsis and rice.

To understand the expansion of multicopy microRNA (miRNA) families in plants, we localized the reported miRNA genes from Arabidopsis and rice to their chromosomes, respectively, and observed that 37% of 117 miRNA genes from Arabidopsis and 35% of 173 miRNA genes from rice were segmental duplications in the genome. In order to characterize whether the expression diversification has occurred among plant multicopy miRNA family members, we designed PCR primers targeting 48 predicted miRNA precursors from 10 families in Arabidopsis and rice. Results from RT-PCR data suggest that the transcribed precursors of members within the same miRNA family were present at different expression levels. In addition, although miR160 and miR162 sequences were conserved in Arabidopsis and rice, we found that the expression patterns of these genes differed between the two species. These data suggested that expression diversification has occurred in multicopy miRNA families, increasing our understanding of the expression regulation of miRNAs in plants.

Arabidopsis↗

PubMed2006

Distribution of 19 major virulence genes in Legionella pneumophila serogroup 1 isolates from patients and water in Queensland, Australia.

The distribution of 19 major virulence genes and the presence of plasmids were surveyed in 141 Legionella pneumophila serogroup (SG) 1 isolates from patients and water in Queensland, Australia. The results showed that 16 of the virulence genes examined were present in all isolates, suggesting that they are life-essential genes for isolates in the environment and host cells. The 65 kb pathogenicity island identified originally in strain Philadelphia-1(T) was detected more frequently in isolates from water (44.2%) than in those from patients (2.7%), indicating that the 65 kb DNA fragment may aid the survival of L. pneumophila in the sampled environment. However, the low frequency of the 65 kb fragment in isolates from patients suggests that the pathogenicity island may not be necessary for L. pneumophila to cause disease. Plasmids were not detected in the L. pneumophila SG1 isolates from patients or water studied. There was an association of both lvh and rtxA with the virulent and predominant genotype detected by amplified fragment length polymorphism, termed AF1, whereas the avirulent common isolate from water termed AF16 did not have lvh or rtxA genes, with the exception of one isolate with rtxA. It was found that a PCR detection test strategy with lvh and rtxA as pathogenesis markers would be useful for determining the infection potential of an isolate.

Australia↗

PubMed2006

Genome-wide analysis of basic/helix-loop-helix transcription factor family in rice and Arabidopsis.

The basic/helix-loop-helix (bHLH) transcription factors and their homologs form a large family in plant and animal genomes. They are known to play important roles in the specification of tissue types in animals. On the other hand, few plant bHLH proteins have been studied functionally. Recent completion of whole genome sequences of model plants Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) allows genome-wide analysis and comparison of the bHLH family in flowering plants. We have identified 167 bHLH genes in the rice genome, and their phylogenetic analysis indicates that they form well-supported clades, which are defined as subfamilies. In addition, sequence analysis of potential DNA-binding activity, the sequence motifs outside the bHLH domain, and the conservation of intron/exon structural patterns further support the evolutionary relationships among these proteins. The genome distribution of rice bHLH genes strongly supports the hypothesis that genome-wide and tandem duplication contributed to the expansion of the bHLH gene family, consistent with the birth-and-death theory of gene family evolution. Bioinformatics analysis suggests that rice bHLH proteins can potentially participate in a variety of combinatorial interactions, endowing them with the capacity to regulate a multitude of transcriptional programs. In addition, similar expression patterns suggest functional conservation between some rice bHLH genes and their close Arabidopsis homologs.

Amino Acid Sequence↗

PubMed2005

Expression and purification of the synthetic preS1 gene of Hepatitis B Virus with preferred Escherichia coli codon preference.

To produce high levels of hepatitis B virus (HBV) preS1 protein at low cost, a DNA fragment encoding the preS1 region, residues 1-119, of HBV adr subtype was synthesized by overlapping-PCR according to Escherichia coli (E. coli) B preferred codon usage. The synthetic preS1 gene (spreS1) was cloned into the bacterial expression vector pET-30a and transferred into the expression strain E. coli BL21(DE3). Recombinant preS1 protein with an N-terminal His6 tag was expressed at high levels in soluble form, yielding about 44% of the total cellular protein. This technique overcomes problems that existed in previously reported expression systems of preS1 or its epitope, i.e., low-level expression or expression in inclusion bodies. Using this His-tagged preS1 expression system, recombinant protein was purified by single-step affinity chromatography on a Ni-NTA column resulting in a yield was about 28 mg recombinant protein per liter culture. Furthermore, Western blotting and indirect ELISA analysis demonstrate that the reactivity of preS1-specific antibody is comparable between the recombinant and commercialized preS1 protein. Thus, our improved expression system could be used for practical, low-cost large-scale production of recombinant preS1 without refolding steps.

Base Sequence↗

PubMed2005

Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives.

4-Hydroxybenzaldehyde (HBA) derivatives were examined as inhibitors for GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). Investigation of structure-activity relation revealed that a carbonyl group or an amino group as well as a hydroxy group at the para position of the benzene ring are important for both enzymes' inhibition. HBA was shown to give competitive inhibition of GABA-T with respect to alpha-ketoglutarate and competitive inhibition of SSADH. 4-Hydroxybenzylamine (HBM) also showed the competitive inhibition on GABA-T with respect to GABA. In conclusion, the inhibitory effects of HBA and HBM on both enzymes could result from the similarity between both molecules and the two enzymes' substrates in structure, as well as the conjugative effect of the benzene ring. This suggested that the presence of the benzene ring may be accepted by the active site of both enzymes, HBA and HBM may be considered as lead compounds to design novel GABA-T inhibitors.

4-Aminobutyrate Transaminase↗

PubMed2005

Better prediction of protein contact number using a support vector regression analysis of amino acid sequence.

BACKGROUND: Protein tertiary structure can be partly characterized via each amino acid's contact number measuring how residues are spatially arranged. The contact number of a residue in a folded protein is a measure of its exposure to the local environment, and is defined as the number of Cbeta atoms in other residues within a sphere around the Cbeta atom of the residue of interest. Contact number is partly conserved between protein folds and thus is useful for protein fold and structure prediction. In turn, each residue's contact number can be partially predicted from primary amino acid sequence, assisting tertiary fold analysis from sequence data. In this study, we provide a more accurate contact number prediction method from protein primary sequence. RESULTS: We predict contact number from protein sequence using a novel support vector regression algorithm. Using protein local sequences with multiple sequence alignments (PSI-BLAST profiles), we demonstrate a correlation coefficient between predicted and observed contact numbers of 0.70, which outperforms previously achieved accuracies. Including additional information about sequence weight and amino acid composition further improves prediction accuracies significantly with the correlation coefficient reaching 0.73. If residues are classified as being either "contacted" or "non-contacted", the prediction accuracies are all greater than 77%, regardless of the choice of classification thresholds. CONCLUSION: The successful application of support vector regression to the prediction of protein contact number reported here, together with previous applications of this approach to the prediction of protein accessible surface area and B-factor profile, suggests that a support vector regression approach may be very useful for determining the structure-function relation between primary protein sequence and higher order consecutive protein structural and functional properties.

Algorithms↗

PubMed2005

The Putative RNA-dependent RNA polymerase RDR6 acts synergistically with ASYMMETRIC LEAVES1 and 2 to repress BREVIPEDICELLUS and MicroRNA165/166 in Arabidopsis leaf development.

The Arabidopsis thaliana ASYMMETRIC LEAVES1 (AS1) and AS2 genes are important for repressing class I KNOTTED1-like homeobox (KNOX) genes and specifying leaf adaxial identity in leaf development. RNA-dependent RNA polymerases (RdRPs) are critical for posttranscriptional and transcriptional gene silencing in eukaryotes; however, very little is known about their functions in plant development. Here, we show that the Arabidopsis RDR6 gene (also called SDE1 and SGS2) that encodes a putative RdRP, together with AS1 and AS2, regulates leaf development. rdr6 single mutant plants displayed only minor phenotypes, whereas rdr6 as1 and rdr6 as2 double mutants showed dramatically enhanced as1 and as2 phenotypes, with severe defects in the leaf adaxial-abaxial polarity and vascular development. In addition, the double mutant plants produced more lobed leaves than the as1 and as2 single mutants and showed leaf-like structures associated on a proportion of leaf blades. The abnormal leaf morphology of the double mutants was accompanied by an extended ectopic expression of a class I KNOX gene BREVIPEDICELLUS (BP) and high levels of microRNA165/166 that may lead to mRNA degradation of genes in the class III HD-ZIP family. Taken together, our data suggest that the Arabidopsis RDR6-associated epigenetic pathway and the AS1-AS2 pathway synergistically repress BP and MIR165/166 for proper plant development.

Arabidopsis↗

PubMed2005

Prediction of protein B-factor profiles.

The polypeptide backbones and side chains of proteins are constantly moving due to thermal motion and the kinetic energy of the atoms. The B-factors of protein crystal structures reflect the fluctuation of atoms about their average positions and provide important information about protein dynamics. Computational approaches to predict thermal motion are useful for analyzing the dynamic properties of proteins with unknown structures. In this article, we utilize a novel support vector regression (SVR) approach to predict the B-factor distribution (B-factor profile) of a protein from its sequence. We explore schemes for encoding sequences and various settings for the parameters used in SVR. Based on a large dataset of high-resolution proteins, our method predicts the B-factor distribution with a Pearson correlation coefficient (CC) of 0.53. In addition, our method predicts the B-factor profile with a CC of at least 0.56 for more than half of the proteins. Our method also performs well for classifying residues (rigid vs. flexible). For almost all predicted B-factor thresholds, prediction accuracies (percent of correctly predicted residues) are greater than 70%. These results exceed the best results of other sequence-based prediction methods.

Algorithms↗

PubMed2005

Determining a maximum-tolerated schedule of a cytotoxic agent.

Most phase I clinical trials are designed to determine a maximum-tolerated dose (MTD) for one initial administration or treatment course of a cytotoxic experimental agent. Toxicity usually is defined as the indicator of whether one or more particular adverse events occur within a short time period from the start of therapy. However, physicians often administer an agent to the patient repeatedly and monitor long-term toxicity due to cumulative effects. We propose a new method for such settings. It is based on the time to toxicity rather than a binary outcome, and the goal is to determine a maximum-tolerated schedule (MTS) rather than a conventional MTD. The model and method account for a patient's entire sequence of administrations, with the overall hazard of toxicity modeled as the sum of a sequence of hazards, each associated with one administration. Data monitoring and decision making are done continuously throughout the trial. We illustrate the method with an allogeneic bone marrow transplantation (BMT) trial to determine how long a recombinant human growth factor can be administered as prophylaxis for acute graft-versus-host disease (aGVHD), and we present a simulation study in the context of this trial.

Algorithms↗

PubMed2005

Factors that influence successful training and faculty career development in hematology/oncology patient-oriented clinical research.

BACKGROUND: We wanted to identify what factors promote career development in patient-oriented clinical research (POCR). METHODS: We used a survey questionnaire covering areas relevant to the training of subspecialty fellows and the career development of POCR faculty. RESULTS: Pursuit of an academic career after fellowship correlated with completion of a clinical project, availability of a clinical research training program, opportunity to earn academic credit, faculty mentorship, and obtaining independent career development funding. Successful faculty career development in POCR was closely correlated with excellent morale and adequate protected time for academic pursuits. CONCLUSIONS: Specific academic environmental factors positively influence success in POCR hematology/oncology fellowship training and faculty career development.

Biomedical Research↗